| First Author | Vernes SC | Year | 2008 |
| Journal | N Engl J Med | Volume | 359 |
| Issue | 22 | Pages | 2337-45 |
| PubMed ID | 18987363 | Mgi Jnum | J:155183 |
| Mgi Id | MGI:4412433 | Doi | 10.1056/NEJMoa0802828 |
| Citation | Vernes SC, et al. (2008) A functional genetic link between distinct developmental language disorders. N Engl J Med 359(22):2337-45 |
| abstractText | BACKGROUND: Rare mutations affecting the FOXP2 transcription factor cause a monogenic speech and language disorder. We hypothesized that neural pathways downstream of FOXP2 influence more common phenotypes, such as specific language impairment. METHODS: We performed genomic screening for regions bound by FOXP2 using chromatin immunoprecipitation, which led us to focus on one particular gene that was a strong candidate for involvement in language impairments. We then tested for associations between single-nucleotide polymorphisms (SNPs) in this gene and language deficits in a well-characterized set of 184 families affected with specific language impairment. RESULTS: We found that FOXP2 binds to and dramatically down-regulates CNTNAP2, a gene that encodes a neurexin and is expressed in the developing human cortex. On analyzing CNTNAP2 polymorphisms in children with typical specific language impairment, we detected significant quantitative associations with nonsense-word repetition, a heritable behavioral marker of this disorder (peak association, P=5.0x10(-5) at SNP rs17236239). Intriguingly, this region coincides with one associated with language delays in children with autism. CONCLUSIONS: The FOXP2-CNTNAP2 pathway provides a mechanistic link between clinically distinct syndromes involving disrupted language. |
